A Study of CC-122 to Assess the Safety and Tolerability in Japanese Patients With Advanced Solid Tumors and Non-Hodgkin's Lymphoma (NHL)

A Phase 1, Multi-center, Open-label Dose-escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of CC-122 Administered Orally to Adult Japanese Subjects With Advanced Solid Tumors or Non-Hodgkin's Lymphoma

To determine the safety and tolerability of CC-122 when administered orally to adult Japanese subjects with advanced solid tumors or Non-Hodgkin's Lymphoma (NHL) and to define the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).

This is a phase 1, multicenter, open-label, dose-escalation study that will evaluate the safety, tolerability, (Pharmacokinetics) PK, and preliminary efficacy of CC-122 in Japanese subjects with advanced solid tumors or Non-Hodgkin's Lymphoma (NHL).

Subjects will receive ascending dose levels of CC-122 from Cycle 1 onwards to measure PK and to determine safety and tolerability.

An initial cohort of at least three subjects will be given CC-122 at a dose of 2.0 mg on an intermittent dosing schedule (5 continuous days out of 7 days per week) and 3-6 subjects will be enrolled in subsequent dose levels. Dose escalation for subsequent cohorts will proceed according to a standard dose escalation design (3+3 design) (Storer, 1989) to establish initial toxicity.

Inclusion Criteria:

1. Understand and voluntarily sign an informed consent document prior to any study-related assessments/procedures are conducted

2. 20 years or older, with histological or cytological confirmation of advanced solid tumors or Non-Hodgkin's Lymphoma (NHL), including those who have progressed on standard anticancer therapy or for whom no other conventional therapy exists

3. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 for all tumors

4. Subjects must have the following laboratory values:

   ・Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L

   • Hemoglobin (Hgb) ≥ 9 g/dL, drawn at least 7 days after the last RBC transfusion
   • Platelets (Plt) ≥ 100 x 109/L, drawn at least 7 days after the last platelet transfusion
   • Potassium within normal limits or correctable with supplements
   • Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN) or ≤ 5.0 x ULN if liver tumors are present
   • Serum bilirubin ≤ 1.5 x ULN; subjects with serum bilirubin >1.5 x ULN and ≤ 2 x ULN may be enrolled if agreed to by the sponsor
   • Serum creatinine ≤ ULN or 24-hour clearance ≥ 50 mL/min
   • Negative serum pregnancy test in females of childbearing potential as per the CC-122 Pregnancy Prevention Rist Management Plan

5. Able to adhere to the study visit schedule and other protocol requirements

6. Must adhere to the Pregnancy Prevention Rist Management Plan

Exclusion Criteria:

1. Subjects with primary central nervous system (CNS) malignancies or symptomatic central nervous system metastases. Subjects with brain metastases that have been previously treated and are stable for 6 weeks are allowed

2. Known acute or chronic pancreatitis

3. Any peripheral neuropathy ≥ NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Grade 2

4. Persistent diarrhea or malabsorption ≥ NCI CTCAE Grade 2, despite medical management

5. Impaired cardiac function or clinically significant cardiac diseases, including any of the following:

   • Left Ventricular Ejection Fraction (LVEF) < 45% as determined by Multiple Gated Acquisition Scan (MUGA) scan or Echocardiogram (ECHO)

   • Complete left bundle branch, or bifascicular block

     • Congenital long QT syndrome
     • Persistent or uncontrolled ventricular arrhythmias or atrial fibrillation
     • QTcF > 460 msec on screening electrocardiogram (ECG) (mean of triplicate recordings)
     • Unstable angina pectoris or myocardial infarction ≤ 3 months prior to starting CC-122
     • Troponin-T value >0.4 ng/mL or Brain Natriuretic Peptide (BNP) >300 pg/mL Subjects with baseline troponin-T >ULN or BNP >100 pg/mL are eligible but must and optimization of cardioprotective therapy.

   • Other clinically significant heart disease such as congestive heart failure requiring treatment or uncontrolled hypertension (blood pressure ≥ 160/95 mmHg)

6. Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 weeks, whichever is shorter, prior to starting CC-122 or who have not recovered from side effects of such therapy. Luteinizing hormone-releasing hormone (LHRH) agonists will be allowed for subjects with metastatic prostate cancer

7. Major surgery ≤ 2 weeks prior to starting CC-122 or still recovering from post operative side effects

8. Women who are pregnant or breast feeding. Adults of reproductive potential not employing two forms of birth control as per Pregnancy Prevention Risk Management Plan (PPRMP)

9. Known human immunodeficiency virus (HIV) infection

10. Known acute or chronic hepatitis B or C virus infection

11. Status post solid organ transplant

12. Less than 100 days for subjects receiving autologous hematologic stem cell transplant (HSCT); or 6 months for subjects receiving allogeneic HSCT, or if otherwise not fully recovered from HSCT-related toxicity

    a. The 6-month exclusionary period for recovery from HSCT-associated toxicity, applies regardless of whether an autologous or allogeneic transplant was performed

13. Known hypersensitivity to any component of the formulation of CC-122

14. Any significant medical condition (including active or controlled infection or renal disease), laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study

15. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study

16. Any condition that confounds the ability to interpret data from the study